Radiosynthesis and in Vivo Evaluation of [11C]MPC-6827, the First Brain Penetrant Microtubule PET Ligand

Abstract

Abnormalities of microtubules (MTs) are implicated in the pathogenesis of many CNS diseases. Despite the potential of an MT imaging agents, no PET ligand is currently available for in vivo imaging of MTs in the brain. We radiolabeled [¹¹C]MPC-6827, a high affinity MTA, and demonstrated its specific binding in rat and mice brain using PET imaging. Our experiments show that [¹¹C]MPC-6827 has specific binding to MT in brain, and it is the first MT-binding PET ligand.

Figure 1.

(A) Baseline biodistribition of [¹¹C]MPC-6827 in male white mice (n = 3). (B) Blocking biodistriution of [¹¹C]MPC-6827 in mice at 30 min (n = 3)

Figure 2.

Sum of 0–60 min microPET sagittal images of [¹¹C]MPC-6827 in a representative mouse brain (left, baseline; right, blocking with 5 mg/kg MPC-6827; cross lines represent center of brain).

Figure 3.

Sum of 0–60 min microPET sagittal images of [¹¹C]MPC-6827 in rat brain (left, transverse; middle, coronal; right, sagittal; cross lines represent center of brain).

Scheme 1.

Synthesis of MPC-6827 and Radiosynthesis of [¹¹C]MPC-6827